Effects of Isotretinoin on the Phosphoinositide-3-kinase/Akt/FoxO1 Pathway and Molecular Functions of SZ95 Sebocytes In vitro
- *Corresponding Author:
- Yasaman Mirdamadi
Department of Dermatology and Venereology
Otto-von Guericke University
Leipziger Str. 44, 39120 Magdeburg, Germany
Tel: +49 3916715240
Fax: +49 391671523
E-mail: [email protected]
Received date: April 14, 2017; Accepted date: May 29, 2017; Published date: June 02, 2017
Citation: Mirdamadi Y, Thielitz A, Wiede A, Goihl A, Zouboulis CC, et al. (2017) Effects of Isotretinoin on the Phosphoinositide-3-kinase/Akt/FoxO1 Pathway and Molecular Functions of SZ95 Sebocytes In vitro. J Clin Exp Dermatol Res 8:399. doi:10.4172/2155-9554.1000399
Copyright: © 2017 Mirdamadi Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: For more than 3 decades, isotretinoin [13-cis retinoic acid (13-cis RA)] is established as the most potent oral treatment for severe acne. However, the molecular mechanisms of isotretinoin action have not been fully elucidated. Recently, we showed that insulin and insulin-like growth factor 1 (IGF-1) increase differentiation and decrease proliferation of SZ95 sebocytes in vitro via activation of the phosphoinositide 3-kinase (PI3K)/Akt/forkhead box-O1 (FoxO1) pathway. Furthermore, this pathway is activated in patient acne biopsies in vivo. Using SZ95 sebocytes as an in vitro model, the aim of this study was to investigate the effect of isotretinoin on PI3K pathway activation.
Methods: SZ95 sebocytes were treated under light protection with 0.1 μM isotretinoin in the presence or absence of 1.0 and 0.1 μM IGF-1 or insulin or 50 μM LY294002 inhibitor in a time- dependent manner. The expression of p-Akt and its downstream target p-FoxO1 was analyzed by Western blot. FoxO transcriptional activity was measured by dual luciferase assay. Nuclear and cytoplasmic mobilization of FoxO1, p-FoxO1, and p-Akt were also determined by immunofluorescence microscopy.Proliferation of sebocytes was measured by [3H]-thymidine incorporation and sebocyte differentiation by oil red O staining.
Results: We show that isotretinoin activates the PI3K/Akt pathway and decreases the nuclear content of FoxO1 and its transcriptional activity in sebocytes in vitro and in sebaceous gland biopsies from an isotretinoin-treated acne patient. Isotretinoin reduces the proliferation of IGF-1- or insulin-stimulated sebocytes more effectively than IGF-1 and insulin alone. However, it normalizes the increased lipid accumulation in IGF-1- or insulin-stimulated sebocytes via a PI3K-independent pathway.
Conclusion: Our data from the SZ95 sebocyte in vitro model suggest that the potent therapeutic effect of isotretinoin in acne is not mediated via the PI3K/Akt/FoxO1 pathway.